npbuilds Modality Trajectory Director
A new target×modality is not a blank slate — it is a point on a curve that twelve prior mechanism classes have already traced. Drug classes obey a stable life-cycle (target ID → tool/platform → first-in-human → first approval → class explosion → maturity) with a ~18–30 year clock to first approval and a compressed 2–5 year explosion once one hard-endpoint pivotal readout lands in a genetically- or biomarker-defined population. This director routes the "where will this go, and will it work?" question to specialists that place a candidate on that arc, find its nearest validated analog, grade its human-genetics validation rung, and decompose an early conviction score. It is the analog engine that consumes the radar's (frontier-intelligence) watchlist and hands a scored thesis to Asclepius's diligence pillars.
Child Skills
| Skill | Type | When to Use |
|---|---|---|
| modality-lifecycle | knowledge | Assessing where a modality sits on its own maturity curve, its delivery bottleneck, and what unlocks the next stage — supplies the P(modality deliverable) term |
| moa-analog-engine | knowledge | Placing a target×modality on the historical MOA arc, finding the nearest validated analog, and naming the still-pending ignition trial to watch — the core placement skill |
| target-validation-ladder | knowledge | Grading how validated a target is on the human-genetics evidence ladder (causality + direction-of-effect), earlier-stage than mechanism-risk-adjuster — supplies the P(biology holds) term |
| frontier-conviction-scorer | knowledge | Decomposing a discovery-stage conviction score (biology × modality × arc-position × timing) anchored to empirical base rates, with explicit handoff to rNPV/PoS once a clinical asset exists |
Routing Logic
| Question Signal | Route To | Examples |
|---|---|---|
| Is this modality ready, delivery problem, where is the modality on its curve, what unlocks it | modality-lifecycle | "Is in-vivo CAR ready, or still a delivery problem?" |
| What's the analog, where on the arc, how long until it matters, what trial to watch, has this pattern happened before | moa-analog-engine | "What's the historical analog for oral PCSK9, and where on the arc is it?" |
| How validated is the target, genetic support, is this causal, will the biology hold | target-validation-ladder | "Grade the human-genetics validation for TREM2 in Alzheimer's" |
| What's my conviction, early PoS, is this worth a position, score this candidate | frontier-conviction-scorer | "Give me a discovery-stage conviction score for amylin agonism in obesity" |
| Modality readiness + arc placement | modality-lifecycle then moa-analog-engine | "Is this modality ready and where does the class sit?" |
| Full trajectory thesis | All four, ending in frontier-conviction-scorer | "Place, grade, and score this candidate" |
Multi-Skill Questions
Where on the arc, and how far will it travel?: "Where is this class, and what happens next?"
- Load moa-analog-engine to find the nearest validated analog, place arc-position, and name the ignition trial to watch
- Load modality-lifecycle to check whether the modality itself is deliverable or still gated by a delivery bottleneck
- Synthesize: a target on a proven arc with an undeliverable modality stalls until the platform fix arrives (siRNA pre-GalNAc); the ignition trial is the event to watch
Will the biology hold?: "Is this target real?"
- Load target-validation-ladder to grade the human-genetics evidence (causality, direction-of-effect, constraint, pleiotropy-as-safety)
- Load moa-analog-engine to check whether the validation pattern matches a genetics-first analog (PCSK9) vs a modality-unlock analog (KRAS)
- Synthesize: genetic support with direction-of-effect concordance is the single strongest pre-clinical predictor (~2.6× relative success); a confounded non-coding hit is not
Score it: "What's my conviction?"
- Load target-validation-ladder for P(biology holds), modality-lifecycle for P(modality deliverable), moa-analog-engine for arc-position and competitive timing
- Load frontier-conviction-scorer to decompose the score against empirical base rates and emit the rNPV handoff trigger
- Synthesize: the score is qualitative and discovery-stage; it hands off to phase-weighted rNPV the moment a clinical asset and indication exist — it never replaces diligence math
Curriculum Order
- modality-lifecycle — Foundation. Learn the maturity map and that delivery, not biology, is usually the binding constraint; that modalities can regress; and that an enabling-platform fix converts a stalled class. This is the P(modality deliverable) term.
- moa-analog-engine — Second, and central. Learn the five-phase arc, the 18–30 year time constant, the three sub-patterns (undruggable-cracking, indication-creep, resistance-ladder), and the ignition-event doctrine. This is how a candidate gets placed and its nearest analog found.
- target-validation-ladder — Third. Learn the human-genetics evidence ladder and why causality + direction-of-effect are load-bearing. This is the P(biology holds) term and the most rigorous gate.
- frontier-conviction-scorer — Last. The synthesizer. With modality readiness, arc-position, and target validation in hand, learn to decompose a base-rate-anchored conviction score and to recognize the handoff point to formal PoS/rNPV.
Conflict Resolution
| Conflict | Resolution | Reason |
|---|---|---|
| target-validation-ladder grades the biology strong but modality-lifecycle says the modality cannot yet reach the target | Conviction is gated by the weaker term; flag as "right target, wrong era — watch for the delivery unlock" | A validated target with an undeliverable modality is a waiting game, not a current bet (siRNA before GalNAc; extrahepatic oligo today) |
| moa-analog-engine places the candidate early on a proven arc but frontier-conviction-scorer's base rates look punishing | Arc-position and analog inform direction; base rates anchor magnitude — report both, do not let optimism override the base rate | The base rate is the prior; the analog adjusts it. De novo optimism is the most common error in early conviction |
| A marquee clinical failure just occurred in the class | Do not auto-kill; check whether a modality re-engineering follows | Anti-amyloid, ADCs, and siRNA all exploded after marquee failures once the modality was re-engineered — failure + re-engineering is a BUY signal |
| target-validation-ladder and mechanism-risk-adjuster disagree | target-validation-ladder governs discovery-stage; mechanism-risk-adjuster governs PoS-stage; hand forward, do not double-count | They are sequential stages of the same evidence, not competing estimates |
Scope Boundaries
This director handles: all questions about placing a target×modality on the historical MOA arc, finding validated analogs, assessing modality maturity and delivery readiness, grading human-genetics target validation, and producing discovery-stage conviction scores.
Route to Asclepius when:
- A clinical asset and indication exist and the question is formal PoS (route to
probability-of-success/pos-calculator) or valuation (route toasset-valuation/rnpv-modeler) - The mechanism needs PoS-stage risk adjustment rather than discovery-stage validation (route to
probability-of-success/mechanism-risk-adjuster) - The question is which emerging targets to scout in the first place (route to
frontier-intelligence) - The question is manufacturing feasibility/COGS for a specific program rather than modality-class readiness (route to
manufacturing-ip)
Cross-Domain Connections
- Biotech-venture/frontier-intelligence: the radar that feeds this engine — ranked candidates flow in from emerging-target-radar
- Biotech-venture/probability-of-success (pos-base-rates, pos-calculator, mechanism-risk-adjuster): the diligence-stage successors; frontier-conviction-scorer anchors to pos-base-rates and hands off to pos-calculator; target-validation-ladder hands off to mechanism-risk-adjuster
- Biotech-venture/asset-valuation/rnpv-modeler: the conviction score becomes an rNPV input once a clinical asset and indication exist
- Biotech-venture/manufacturing-ip/modality-manufacturing: modality-lifecycle's delivery-readiness view complements modality-specific manufacturing/COGS analysis
- Research/spelunker: deep verification of a historical arc, an analog claim, or a target's genetic support
- Probability-of-success base rates: the empirical anchor that keeps conviction scores honest against de novo optimism
- Dual use: serves a clinical-scientist learning how mechanism classes mature and an investor sizing early conviction before a clinical readout prices it in